CN1282246A - 速溶性药用组合物 - Google Patents
速溶性药用组合物 Download PDFInfo
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- CN1282246A CN1282246A CN98812372A CN98812372A CN1282246A CN 1282246 A CN1282246 A CN 1282246A CN 98812372 A CN98812372 A CN 98812372A CN 98812372 A CN98812372 A CN 98812372A CN 1282246 A CN1282246 A CN 1282246A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/499—Spiro-condensed pyrazines or piperazines
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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Abstract
一种速溶性药用组合物,包含研磨成微粉末状的(R)－2－(4－溴－2－氟苄基)－1,2,3,4－四氢吡咯并[1,2－a]吡嗪－4－螺－3′－吡咯烷－1,2′,3,5′－四酮(称为AS－3201)。它的溶解度得到改善,并具有良好的生物有效度。
Description
技术领域
本发明是关于(R)-2-(4-溴-2-氟苄基)-1，2，3，4-四氢吡咯并〔1，2-a〕吡嗪-4-螺-3′-吡咯烷-1，2′，3，5′-四酮(此后被称为“AS-3201”)的速溶性药用组合物，此化合物具有很强醛糖还原酶抑制活性。
技术背景
AS-3201是如下结构式的化合物。在日本专利No.2516147(USP 5258382)的实施例22，JP-A-6-192222的参考实施例12(Chem.Abstr.，122，9860(1995))，以及JP-A-8-176105的实验(Chem.Abstr.125，221569(1996))中，都描述了该化合物，它们还公开了该化合物具有很强的醛糖还原酶抑制活性。
日本专利No.2516147(USP 5258382)的实施例28叙述了制备AS-3201片剂的具体方法。即，按常规方法，将AS-3201(1g)，玉米淀粉(25g)，乳糖(58g)，结晶纤维素(11g)，羟丙基纤维素(3g)，轻质无水硅酸(1g)和硬脂酸镁(1g)混合，制成颗粒，并制成每片重100mg的片剂1，000片。
在研究制备具有良好生物有效度的、含有AS-3201的药用组合物方法的过程中，本发明者发现，在低pH的范围内，该物质的水溶解度非常低，达到几μg/ml的程度，因此，在不同的给药个体中，AS-3201的血浆浓度变化很大。
在这种情况下，本发明者作了进一步深入的研究，并发现，通过在组合物中使用微粉化的AS-3201，使组合物中该物质的溶出特性显著地改善了，结果可以得到含有AS-3201的具有良好生物有效度的速溶性药用组合物，从而最后完成了本发明。
本发明的叙述
本发明提供了一种含有微粉化AS-3201的速溶性药用组合物。
对本说明书中使用的一些术语解释如下。
“微粉化AS-3201”意指具有平均颗粒大小＜20μm的AS-3201粉末。“平均微粒大小”意指在基于重量或体积，在累积性微粒分布中50％的微粒大小(参阅，HA Lieberman等，“Pharmaceutical DosageForms：Tablets”，Marcel Dekker，Inc，纽约，1990，vol.2，174-186；Kouichi IINOYA(编著)“粉末和微粒测定手册(日文)”，NIKKAN KOGYO SHINBIN 公司，1981，29-36)。“溶出度试验”意指按照第十二版日本药典中指定的Paddle方法(50 rpm)，从相当于20mg AS-3201含量的待测药用组合物中测定AS-3201的溶出度，用0.2M磷酸缓中液(pH 6.5，900ml)作试验溶液，用分光光度法在300nm处测定AS-3201。“pKal”的含义是，一种酸性物质在其无限稀释的溶液中，在25℃的酸离解指数。当一种酸性物质是多元酸时，它意指第一步离解的酸离解指数。“水溶解度”意指在100ml水中被溶解溶质的最大量。名词“大约”打算用于包含下述术语的数值。
微粉化AS-3201的平均微粒大小优选小于大约10μm，更优选小于约5μm，最优选在大约0.5μm-3μm之间。
按照日本专利No.2516147(USP 5258382)中公开的方法，通常可获得具有平均微粒大小约60μm-120μm的AS-3201结晶体。使用常规用于制药领域的研磨机，可以将AS-3201结晶微粉化。研磨机包括例如，液体动力研磨机如Jet Mill(日本SEISHIN ENTERPRISE公司制造)，高速旋转冲击研磨机如Sample Mill(日本HosokawMicron公司制造)，Pin Mill(德国ALPINE制造)，或Angmill(日本Hosokawa Micron公司制造)，湿式高速滚筒磨粉研磨机如Micros(日本Nara机械公司制造)，以及滚筒式研磨机如球磨研磨机。为了获得具有小于约5μm平均微粒大小的微粉化粉末，液体动力研磨机是优选的。微粉化可对AS-3201结晶体单独进行，或者可对AS-3201结晶体和用于制备药物组合物的部分或全部药物赋形剂或载体的混合物进行。
本发明含有AS-3201的速溶性药用组合物可以是固体剂型，包括例如，片剂，胶囊剂，颗粒剂和粉剂等。按常规的方法，通过将微粉化的AS-3201用药用赋形剂或载体如稀释剂，崩解剂，粘合剂和润滑剂相混合，可制备这些药物组合物。例如，通过湿式制粒法如高剪切力制粒，液化床制粒，搅拌式流化床制粒，离心式流化床制粒或挤压制粒，或者通过干式制粒法如滚筒压制或击块制粒(rollercompaction or Slugging)，将混合物制成颗粒，然后将形成的颗粒装入胶囊制成胶囊剂，或者压制成片剂。按另一种方式，也可将微粉化的AS-3201和药物赋形剂或载体直接装入胶囊制成胶囊剂，或者压制成片剂。还可任选对这些药物组合物包衣，或者组合物中还可以含有稳定剂，表面活性剂，着色剂和香味剂等。
除了显示与AS-3201具有不良配伍性的之外，可使用任何一种药用赋形剂或载体。稀释剂包括例如，乳糖，淀粉，结晶纤维素，D-甘露醇，蔗糖，葡萄糖，赤藓醇，木糖醇，D-山梨醇，二价无水磷酸钙和硫酸钙。崩解剂包括例如，淀粉，结晶纤维素，低取代的羟丙基纤维素，羧甲醚纤维素，羧甲醚纤维素钙，羧甲基淀粉钠，交联羧甲基纤维素钠，部分预凝胶化淀粉和羟丙基淀粉。粘合剂包括例如，阿拉伯胶，淀粉，羟丙基纤维素，羟丙基甲基纤维素，聚乙烯醇，聚麦芽三糖，明胶，乙基纤维素，甲基纤维素，羧甲醚纤维素钠和糊精。润滑剂包括例如，硬脂酸镁，硬脂酸钙，硬脂酸，脂肪酸蔗糖酯，轻质无水硅酸，滑石粉，氢化油和聚乙二醇。
稳定剂可以是具有比AS-3201更强酸性，即pKa=5.6-5.8的任何药学上适用的酸性物质。而优选的酸性物质是具有pKal小于大约4.5，在15℃-25℃水溶解度大于约10g/100ml的酸性物质。更优选的酸性物质是具有pKal小于大约33，在15℃-25℃水溶解度大于约50g/100ml的酸性物质。特别优选的酸性物质包括例如，柠檬酸，酒石酸，马来酸和磷酸。在这些酸性物质中，酒石酸是最优选的。酸性物质的含量优选在大约0.5％-2.5％重量范围之内。在制备含有AS-3201的药用组合物情况下，加入小于大约5％重量比例的稳定剂是较好的。
用于本发明药用组合物的表面活性剂包括例如，脱水山梨糖醇脂肪酸酯和聚山梨酸酯。着色剂包括例如焦油染料，焦糖和红色氧化铁。香味剂包括例如增甜剂和香料。
通过使用微粉化的AS-3201，可显著地改善此有效物质从组合物中的溶出特性，并且，通过进一步调整药用赋形剂或载体的组合比例，可获得具有更加改善的溶出特性，以及具有良好生物有效度的含有AS-3201的速溶性药用组合物。药物赋形剂或载体的组合比例，可取决于AS-3201的含量而改变。在本发明速溶性药用组合物中AS-3201的含量，相对于药用组合物总重量通常是在大约0.5％-25％范围内。相对于药用组合物总重量，当AS-3201的含量在大约0.5％-5％范围内时，那末，该药用组合物通常含有按重量计大约51％-93.8％比例的稀释剂，大约5％-35％比例的崩解剂，大约0.5％-5％比例的粘合剂，以及大约0.2％-4％比例的润滑剂。更优选的是，本药用组合物含有按重量计大约59％-88％比例的稀释剂，大约10％-30％比例的崩解剂，大约1％-3％比例的粘合剂，以及大约0.5％-3％比例的润滑剂。相对于药用组合物的总重量，当AS-3201的含量是大于5％而小于大约25％时，那末该组合物通常含有按重量计大约16％-84.3％比例的稀释剂，大约10％-50％比例的崩解剂，大约0.5％-5％比例的粘合剂，以及大约0.2％-4％比例的润滑剂。更优选的是按重量计大约29％-73.5％比例的稀释剂，大约20％-40％比例的崩解剂，大约1％-3％比例的粘合剂，以及大约0.5％-3％比例的润滑剂。
因为在低pH范围内AS-3201具有极低的水溶解度，达到每毫升几微克的程度，所以，在含有AS-3201的药用组合物的起始溶出速度与其生物有效度之间存在相互关联，具有较快起始溶出速度的组合物可以表现出较好的生物有效度。根据以上观点，优选的组合物是在开始溶出试验之后15分钟内，其有效物质具有50％或更高的溶出百分率的组合物，更优选的药用组合物是在开始溶出试验之后15分钟内，具有80％或更高的溶出百分率的组合物。
如果有必要，可将本发明含有AS-3201的速溶性药用组合物包装在低湿气通透性材料的药瓶内，或者包装在防水包装如热封包装内。
附图简述
图1是显示实施例1和2，以及比较实施例1的片剂溶出度的曲线图。
实施本发明的最佳方式
通过实施例和比较实施例对本发明作更详细的说明，但是不应该认为本发明仅限于这些内容。应用激光衍射微粒大小分布分析仪(HELOS & RODOS(商标)，德国SYMPATEC GmbH制造)测定平均微粒大小，并通过干空气弥散法(弥散空气压力：0.5atm)根据体积的累积微粒分布进行计算。
实施例1
制备片剂：
AS-3201 160g
酒石酸 8g
乳糖 492g
低取代的羟丙基纤维素 300g
羟丙基纤维素 20g
硬脂酸镁 20g
总量 1000g
使用Single Truck Jet Mill(SEISHIN ENTERPRISE公司制造，此后缩写为(“Jet Mill”))，以压力6 kgf／cm2的压缩空气，将AS-3201结晶体制成微粉末，得到具有平均微粒大小大约1.5μm的粉末。将这样得到的微粉化AS-3201粉末，乳糖和低取代的羟丙基纤维素装入流化床制粒机和干燥器内，然后通过对其喷雾以5％羟丙基纤维素水溶液中配制的酒石酸溶液，将上述混合物制成颗粒。使此颗粒干燥，并加入硬脂酸镁，然后将此混合物在V型混合器内混合。将此形成物在旋转式压片机上压片，得到片重125mg的片剂，每片含AS-3201 20mg。
实施例2制备片剂：
用Sample Mill(Hosokawa Micron公司制造)将AS-3201结晶体制成微粉末，得到具有平均微粒大小约10μm的粉末。用与实施例1中相同的方式将这样得到的微粉化AS-3201粉末制成颗粒，干燥并压片，得到片重125mg的片剂，每片含AS-3201 20mg。比较实施例1
制备片剂：
用与实施例1中相同的方式，将具有平均微粒大小约87μm的未微粉化的AS-3201结晶体制成颗粒，干燥并压片，得到每片重125mg的片剂，每片含AS-3201 20mg。实验1溶出试验：
按照在第十二版日本药典中所指定的Paddle法(50rpm)，用0.2M磷酸缓冲液(pH 6.5，900ml)作试验溶液，测定实施例1和2，以及比较实施例1片剂中有效物质的溶出度。借助于分光光度法，在300nm处对AS-3201作定量测定。
结果显示在图1中，图1中的每个点表示对实施例1，实施例2和比较实施例1的每种片剂三次重复测定结果的平均值。
如在图1中所示，与比较实施例1的片剂相比较，实施例1和实施例2的片剂具有明显改善的溶出度。
实施例3制备片剂：
AS-3201 160g
酒石酸 10g
乳糖 600g
低取代的羟丙基纤维素 200g
羟丙基纤维素 20g
硬脂酸镁 10g
总量 1000g
用与实施例1中相同的方法处理上述成分，并压片，得到每片重125mg的片剂，每片含AS-3201 20mg。在溶出试验开始之后15分钟内，从这样得到的片剂中有效物质的溶出百分率是72.6％。
实施例4制备片剂：
AS-3201 20g
酒石酸 8g
乳糖 732g
低取代的羟丙基纤维素 200g
羟丙基纤维素 20g
硬脂酸镁 20g
总量 1000g
用Jet Mill，以压力6 kgf/cm2的压缩空气，将AS-3201结晶体制成微粉末，将此形成物连同乳糖和低取代的羟丙基纤维素一起装入流化床制粒机和干燥器，然后，通过对其喷雾以5％羟丙基纤维素水溶液配制的酒石酸溶液，将上述混合物制成颗粒。使颗粒干燥，并对其加入硬脂酸镁，在V型混合器中混合。在旋转制片机上将此形成物压片，得到每片重125mg的片剂，每片含AS-3201 2.5mg。
溶出试验开始之后15分钟内，从这样得到的片剂中有效物质的溶出百分率是93.0％。
实施例5制备片剂：
AS-3201 80g
酒石酸 4g
乳糖 246g
低取代的羟丙基纤维素 150g
羟丙基纤维素 10g
硬脂酸镁 10g
总量 500g
用Jet Mill，以压力6 kgf/cm2的压缩空气，将AS-3201结晶体制成微粉末，加入乳糖和低取代的羟丙基纤维素，然后在VersatileMixer内将形成的混合物混合5分钟。对此混合物加入以4％羟丙基纤维素水溶液配制的酒石酸溶液，并再将此混合物混合10分钟。使此混合物干燥，并加入硬脂酸镁，然后在单冲制片剂上将形成的混合物压片，得到每片重125mg的片剂，每片含AS-3201 20mg。
在开始溶出试验之后15分钟内，从这样得到的片剂中有效物质的溶出百分率为93.2％。
实施例6制备片剂：
AS-3201 144g
乳糖 549g
低取代的羟丙基纤维素 180g
羟丙基纤维素 18g
硬脂酸镁 9g
总量 900g
用Jet Mill，以压力6 kgf／cm2 的压缩空气将AS-3201结晶体制成微粉末，并将此形成物与乳糖和低取代的羟丙基纤维素一起装入流化床制粒机和干燥器内，然后，通过对其喷雾5％羟丙基纤维素水溶液，将上述混合物制成颗粒。干燥之后，加入硬脂酸镁，并将此混合物在V型混合器中混合。在旋转式制片机上将此形成物压片，得到每片重125mg的片剂，每片含AS-3201 20mg。
在开始溶出试验之后15分钟内，从这样得到的片剂中有效物质的溶出百分率为92.0％。
实施例7-9制备片剂：
实施例7 实施例8 实施例9
AS-3201 40g 40g 40g
酒石酸 8g 8g 8g
乳糖 712g 672g 632g
低取代的羟
丙基纤维素 200g 240g 280g
羟丙基纤维素 20g 20g 20g
硬脂酸镁 20g 20g 20g
总量 1000g 1000g 1000g
以同实施例1中相同的方式，将使用Jet Mill制成微粉末的AS-3201制成颗粒，干燥并压片，得到每片重125mg的片剂，每片含AS-3201 5mg。
在开始溶出试验之后15分钟内，从实施例7，8和9片剂中有效物质的溶出百分率分别为91.0％，94.5％和92.7％。实施例10-12制备片剂：
实施例10 实施例11 实施例12
AS-3201 80g 80g 80g
酒石酸 8g 8g 8g
乳糖 672g 632g 592g
低取代的羟
丙基纤维素 200g 240g 280g
羟丙基纤维素 20g 20g 20g
硬脂酸镁 20g 20g 20g
总量 1000g 1000g 1000g
以同实施例1中相同的方式，将使用Jet Mill制成微粉末的AS-3201制成颗粒，干燥并压片，得到每片重125mg的片剂，每片含AS-3201 10mg。
在溶出试验开始之后15分钟内，从实施例10，11和12的片剂中有效物质的溶出百分率分另为89.4％，91.6％和92.2％。
产业适用性
如上面所阐述，本发明含有AS-3201的速溶性药用组合物，具有改善的溶出特性以及良好的生物有效度。
Claims (12)
1．一种速溶性药用组合物，该组合物含有微粉化的(R)-2-(4-溴-2-氟苄基)-1，2，3，4-四氢吡咯并〔1，2-a〕吡嗪-4-螺-3′-吡咯烷-1，2′，3，5′-四酮(此后被称为“AS-3201”)。
2．权利要求1所述速溶性药用组合物，其中微粉化AS-3201的平均微粒大小＜约10μm。
3．权利要求1所述速溶性药用组合物，其中微粉化AS-3201的平均微粒大小＜约5μm。
4．权利要求1所述速溶性药用组合物，其中微粉化AS-3201的平均微粒大小在大约0.5μm-3μm的范围内。
5．权利要求1-4中任何之一所述速溶性药用组合物，它含有相对于该药用组合物的重量大约0.5％-5％重量比例的微粉化AS-3201，大约51％-93.8％重量比例的稀释剂，大约5％-35％重量比例的崩解剂，大约0.5％-5％重量比例的粘合剂，以及大约0.2％-4％重量比例的润滑剂。
6．权利要求5所述速溶性药用组合物，它含有按重量计大约59％-88％重量比例的稀释剂，大约10％-30％重量比例的崩解剂，大约1％-3％重量比例的粘合剂，以及大约0.5％-3％重量比例的润滑剂。
7．权利要求1-4中任何之-所述速溶性药用组合物，它含有相对于该药用组合物总重量大于5％-小于约25％重量比例的微粉化AS-3201，大约16％-84.3％重量比例的稀释剂，大约10％-50％重量比例的崩解剂，大约0.5％-5％重量比例的粘合剂，以及大约0.2％-4％重量比例的润滑剂。
8．权利要求7所述速溶性药用组合物，它含有按重量计大约29％-73.5％重量比例的稀释剂，大约20％-40％重量比例的崩解剂，大约1％-3％重量比例的粘合剂，以及大约0.5％-3％重量比例的润滑剂。
9．权利要求1-8中任何之一所述速溶性药用组合物，在开始溶出试验之后15分钟内，其有效物质具有50％或更高的溶出百分率。
10．权利要求9所述速溶性药用组合物，在开始溶出试验之后15分钟内，其有效物质具有80％或更高的溶出百分率。
11．权利要求1-10中任何之一所述速溶性药用组合物，它包含具有比AS-3201更强酸性的，作为稳定剂的至少一种酸性物质。
12．权利要求11所述速溶性药用组合物，其中的酸性物质选自柠檬酸，酒石酸，马来酸和磷酸中的一种。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30663597 | 1997-10-20 | ||
| JP306635/1997 | 1997-10-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1282246A true CN1282246A (zh) | 2001-01-31 |
| CN1156277C CN1156277C (zh) | 2004-07-07 |
Family
ID=17959478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB98812372XA Expired - Fee Related CN1156277C (zh) | 1997-10-20 | 1998-10-15 | 速溶性药用组合物 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US7141249B2 (zh) |
| EP (1) | EP1033132B1 (zh) |
| KR (1) | KR100571614B1 (zh) |
| CN (1) | CN1156277C (zh) |
| AT (1) | ATE296101T1 (zh) |
| AU (1) | AU740299B2 (zh) |
| BR (1) | BR9814090A (zh) |
| CA (1) | CA2306883C (zh) |
| CZ (1) | CZ299018B6 (zh) |
| DE (1) | DE69830333T2 (zh) |
| ES (1) | ES2242298T3 (zh) |
| HK (1) | HK1030359A1 (zh) |
| HU (1) | HUP0004132A3 (zh) |
| ID (1) | ID23915A (zh) |
| NO (1) | NO319049B1 (zh) |
| NZ (1) | NZ503796A (zh) |
| PL (1) | PL191533B1 (zh) |
| PT (1) | PT1033132E (zh) |
| RU (1) | RU2203665C2 (zh) |
| TR (1) | TR200001056T2 (zh) |
| TW (1) | TW592728B (zh) |
| WO (1) | WO1999020277A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769809A (zh) * | 2014-12-23 | 2016-07-20 | 上海星泰医药科技有限公司 | 提高生物利用度的雷尼司他及其制备方法 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU740299B2 (en) * | 1997-10-20 | 2001-11-01 | Dainippon Sumitomo Pharma Co., Ltd. | Fast-dissolving pharmaceutical composition |
| DK1884242T3 (da) | 2005-05-26 | 2013-05-06 | Dainippon Sumitomo Pharma Co | Farmaceutisk sammensætning omfattende lurasidon |
| EP2327406A4 (en) | 2008-08-14 | 2014-04-09 | Kyorin Seiyaku Kk | STABILIZED PHARMACEUTICAL COMPOSITION |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK607188A (da) * | 1987-11-02 | 1989-06-22 | Merck & Co Inc | Tablet indeholdende en phthalazineddikesyreforbindelse |
| TW202450B (zh) | 1991-06-26 | 1993-03-21 | Dainippon Pharmaceutical Co | |
| JPH0518672A (ja) * | 1991-07-09 | 1993-01-26 | Daido Steel Co Ltd | 熱処理炉の冷却域における炉体構造 |
| DE4141351A1 (de) * | 1991-12-14 | 1993-06-17 | Basf Ag | Stabile pulverfoermige vitamin- und/oder carotinoid-praeparate und verfahren zu deren herstellung |
| DE4400464A1 (de) * | 1994-01-11 | 1995-07-13 | Bayer Ag | Endoparasitizide Mittel |
| DE4440337A1 (de) * | 1994-11-11 | 1996-05-15 | Dds Drug Delivery Services Ges | Pharmazeutische Nanosuspensionen zur Arzneistoffapplikation als Systeme mit erhöhter Sättigungslöslichkeit und Lösungsgeschwindigkeit |
| TW438587B (en) * | 1995-06-20 | 2001-06-07 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
| US6458811B1 (en) * | 1996-03-26 | 2002-10-01 | Eli Lilly And Company | Benzothiophenes formulations containing same and methods |
| AU740299B2 (en) * | 1997-10-20 | 2001-11-01 | Dainippon Sumitomo Pharma Co., Ltd. | Fast-dissolving pharmaceutical composition |
| DK1038525T3 (da) * | 1997-10-20 | 2004-08-02 | Dainippon Pharmaceutical Co | Stabiliseret farmaceutisk præparat af tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3'-pyrrolidin |
-
1998
- 1998-10-15 AU AU94619/98A patent/AU740299B2/en not_active Ceased
- 1998-10-15 BR BR9814090-6A patent/BR9814090A/pt not_active Application Discontinuation
- 1998-10-15 US US09/529,715 patent/US7141249B2/en not_active Expired - Fee Related
- 1998-10-15 EP EP98947883A patent/EP1033132B1/en not_active Expired - Lifetime
- 1998-10-15 CA CA002306883A patent/CA2306883C/en not_active Expired - Fee Related
- 1998-10-15 ES ES98947883T patent/ES2242298T3/es not_active Expired - Lifetime
- 1998-10-15 PT PT98947883T patent/PT1033132E/pt unknown
- 1998-10-15 NZ NZ503796A patent/NZ503796A/en not_active IP Right Cessation
- 1998-10-15 PL PL340045A patent/PL191533B1/pl not_active IP Right Cessation
- 1998-10-15 CN CNB98812372XA patent/CN1156277C/zh not_active Expired - Fee Related
- 1998-10-15 WO PCT/JP1998/004658 patent/WO1999020277A1/ja active IP Right Grant
- 1998-10-15 HU HU0004132A patent/HUP0004132A3/hu unknown
- 1998-10-15 CZ CZ20001418A patent/CZ299018B6/cs not_active IP Right Cessation
- 1998-10-15 RU RU2000112538/14A patent/RU2203665C2/ru not_active IP Right Cessation
- 1998-10-15 AT AT98947883T patent/ATE296101T1/de active
- 1998-10-15 KR KR1020007004191A patent/KR100571614B1/ko not_active IP Right Cessation
- 1998-10-15 ID IDW20000676A patent/ID23915A/id unknown
- 1998-10-15 TR TR2000/01056T patent/TR200001056T2/xx unknown
- 1998-10-15 DE DE69830333T patent/DE69830333T2/de not_active Expired - Lifetime
- 1998-10-19 TW TW087117258A patent/TW592728B/zh not_active IP Right Cessation
-
2000
- 2000-04-18 NO NO20002049A patent/NO319049B1/no not_active IP Right Cessation
-
2001
- 2001-01-29 HK HK01100617A patent/HK1030359A1/xx not_active IP Right Cessation
-
2006
- 2006-08-03 US US11/498,147 patent/US20060269599A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769809A (zh) * | 2014-12-23 | 2016-07-20 | 上海星泰医药科技有限公司 | 提高生物利用度的雷尼司他及其制备方法 |
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Owner name: NIPPO SUMITOMO PHARMACEUTICALS CO., LTD. Free format text: FORMER NAME OR ADDRESS: DAINIPPON PHARMACEUTICAL CO., LTD. |
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Address after: Osaka City, Osaka of Japan Patentee after: Dainippon Sumitomo Pharma Co., Ltd. Address before: Osaka City, Osaka of Japan Patentee before: Dainippon Pharmaceutical Co., Ltd. |
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